Ординатура / Офтальмология / Английские материалы / Atlas of Fundus Autofluorescence Imaging_Holz, Schmitz-Valckenberg, Spaide, Bird_2007
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Frank G. Holz · Steffen Schmitz-Valckenberg · Richard F. Spaide · Alan C. Bird
Atlas of Fundus Autofluorescence Imaging
Frank G. Holz · Steffen Schmitz-Valckenberg Richard F. Spaide · Alan C. Bird (Eds.)
Atlas of Fundus
Autofluorescence
Imaging
With 132 Figures and 1 Table
123
Prof. Dr. med. Frank G. Holz |
Richard F. Spaide, MD |
Department of Ophthalmology |
Professor of Ophthalmology |
University of Bonn |
Vitreous, Retina Macula |
Ernst-Abbe-Str. 2 |
Consultants of New York |
53127 Bonn |
460 Park Ave., 5th Floor |
Germany |
New York, NY 10022 |
|
USA |
Dr. med. Steffen Schmitz-Valckenberg |
Alan C. Bird, MD |
Department of Ophthalmology |
Professor of |
University of Bonn |
Medical Ophthalmology |
Ernst-Abbe-Str. 2 |
Institute of Ophthalmology |
53127 Bonn |
University College London |
Germany |
11–43 Bath Street |
|
London EC1V 9EL |
|
United Kingdom |
Library of Congress Control Number: 2007931906
ISBN 978-3-540-71993-9 Springer Berlin Heidelberg New York
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Preface
It has been known for many years from histopathological studies that autofluorescence is present in the retinal pigment epithelium (RPE) due to the presence of lipofuscin. The demonstration that the excitation spectrum of the “orange-red” fluorophores extends into the visible range indicated that imaging of lipofuscin was accessible to in vivo excitation. However, in vivo recording in humans of autofluorescence using spectrophotometric techniques and imaging with a scanning laser ophthalmoscope are relatively recent.
It is believed that the level of autofluorescence represents a balance between accumulation and clearance of lipofuscin. Accumulation of fluorescent material in the RPE reflects the level of metabolic activity, which is largely determined by the quantity of photoreceptor outer segment renewal. Abnormally high levels are thought to be due to RPE cell dysfunction or to the RPE’s being subjected to an abnormal metabolic load as occurs in Stargardt disease, in which the discs contain abnormally high levels of N-retinylidene-N-retinylethanolamine (A2-E). Evidence of clearance is derived from the observation that outer retinal degeneration is associated with decreased autofluorescence. This could be due to a variety of factors. There appears to be constant degradation of residual bodies in the RPE. There is evidence of photodegradation of A2-E, and in addition, long-term phagolysosomes may be discharged from the RPE cells into the extracellular space.
It is now clear that autofluorescence imaging is useful for diagnosis in patients with visual loss and that certain inherited disorders have distinctive patterns of change.
Perhaps more important is the ability to assess the state of the RPE/photoreceptor complex in ageing. Until recently the only index of ageing was the state of Bruch’s membrane as indicated by the number, size, and distribution of drusen. It is now possible to assess changes in the RPE, and it has been recognised for some years that the RPE plays a crucial role in the pathogenesis of age-related macular disease (AMD). It has been shown that the pattern of autofluorescence varies among patients. However, there is marked symmetry between the eyes of those with bilateral early AMD, implying that autofluorescence characteristics reflect the risk factors, whether genetic or environmental. Furthermore, it is believed that geographic atrophy is preceded by focal increases in autofluorescence, and this belief has given rise to concepts regarding pathological processes in this form of late disease. Lipofuscin is a free radical
Preface
generator when illuminated with blue light. It also acts as a surfactant that causes leakage of membranes and a rise in the pH of phagolysosomes, with consequent predictable loss of activity of degradative enzymes. In turn, lack of recycling from phagosomes may result in lack of material for outer segment renewal and photoreceptor cell death. Of perhaps the greatest importance is the ability to verify the integrity of the RPE/photoreceptor complex prior to treatment of choroidal neovascularisation such that the likely therapeutic outcome may be determined. This can be verified on the basis of autofluorescence imaging. If it is shown that therapeutic benefit can be predicted by autofluorescence imaging, it should become a routine part of the management of such cases, particularly in light of the therapeutic results of the new biological agents.
The value of autofluorescence imaging to clinical practice has been shown beyond any doubt, although, as with many new techniques, the clinical value of the technique has yet to be fully understood. It gives information that is of major clinical importance but is not yet accessible by any other technique.
In this book the principles of autofluorescence imaging are explained, the scope of the technique is summarised, and its application in clinical practice is illustrated. It is hoped that this information will help make the technique more widely available and of greater value to the clinician.
London, Juli 2007
Alan C. Bird
Contents
Part I |
Methodology .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
1 |
1 |
Lipofuscin of the Retinal Pigment Epithelium . . . . . . . . . . . . . . . . . . . . |
|
3 |
|
Janet R. Sparrow |
|
|
1.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
3 |
1.2 |
The Source of RPE Lipofuscin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
3 |
1.3 |
Characteristics of Known RPE Lipofuscin Pigments .. . . . . . . . . . . . . . . . |
|
4 |
1.4 |
Adverse Effects of RPE Lipofuscin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
8 |
1.5 |
Modulators of RPE Lipofuscin Formation . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
9 |
1.6 |
Summary .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
10 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
11 |
2 |
Origin of Fundus Autofluorescence .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
17 |
|
François Delori, Claudia Keilhauer, Janet R. Sparrow, |
|
|
|
Giovanni Staurenghi |
|
|
2.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
17 |
2.2 |
Spectrofluorometry of Fundus Autofluorescence (FAF) .. . . . . . . . . . . . . |
|
18 |
2.3 |
Imaging of FAF .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
18 |
2.4 |
Influence of Crystalline Lens Absorption .. . . . . . . . . . . . . . . . . . . . . . . . . . |
|
19 |
2.5 |
Spatial Distribution of FAF .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
19 |
2.6 |
Spectral Properties of FAF .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
21 |
2.7 |
Age Relationship of FAF .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
23 |
2.8 |
Near-Infrared FAF .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
24 |
2.9 |
Conclusions .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
25 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
25 |
3 |
Fundus Autofluorescence Imaging with the Confocal |
|
|
|
Scanning Laser Ophthalmoscope .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
31 |
|
Steffen Schmitz-Valckenberg, Fred W. Fitzke, Frank G. Holz |
|
|
3.1 |
The Confocal Scanning Laser Ophthalmoscope (cSLO) .. . . . . . . . . . . . . |
|
31 |
3.2 |
FAF Imaging with the cSLO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
31 |
3.3Combination of cSLO Imaging with Spectral-Domain
Optical Coherence Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
34 |
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
36 |
VI |
Contents |
|
|
4 |
How To Obtain the Optimal Fundus Autofluorescence Image |
|
|
|
with the Confocal Scanning Laser Ophthalmoscope .. . . . . . . . . . . . . . |
|
37 |
|
Steffen Schmitz-Valckenberg, Vy Luong, Fred W. Fitzke, Frank G. Holz |
|
|
4.1 |
Basic Considerations .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
37 |
4.2 |
Reflectance Before Autofluorescence Imaging .. . . . . . . . . . . . . . . . . . . . . . |
|
37 |
4.3 |
Image Alignment and Calculation of Mean Image .. . . . . . . . . . . . . . . . . . |
|
39 |
4.4 |
Normalizing of FAF Image . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
39 |
4.5 |
Standardized Protocol for FAF Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
40 |
4.6 |
Pitfalls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
41 |
4.6.1 |
Focus .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
41 |
4.6.2 |
Detector Sensitivity .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
41 |
4.6.3 |
Distance of Laser Scanning Camera to Cornea .. . . . . . . . . . . . . . . . . . . . . |
|
43 |
4.6.4 |
Illumination .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
43 |
4.6.5 |
Image Orientation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
43 |
4.6.6 |
Eye Movements .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
44 |
4.7 |
Media Opacities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
45 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
47 |
5 |
Autofluorescence Imaging with the Fundus Camera .. . . . . . . . . . . . . . |
|
49 |
|
Richard F. Spaide |
|
|
5.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
49 |
5.2 |
Imaging Autofluorescence with a Fundus Camera .. . . . . . . . . . . . . . . . . . |
|
49 |
5.3Differences Between the Autofluorescence Images
|
Taken with a Fundus Camera and a cSLO . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
51 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
53 |
6 |
Macular Pigment Measurement—Theoretical Background . . . . . . . . |
|
55 |
|
Sebastian Wolf, Ute E.K. Wolf-Schnurrbusch |
|
|
6.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
55 |
6.2 |
Functional and Physiological Properties of Macular Pigment . . . . . . . . |
|
55 |
6.3 |
Detection of Macular Pigment .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
56 |
6.4 |
Measurement of Macular Pigment Density Using a cSLO .. . . . . . . . . . . |
|
58 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
59 |
7 |
Macular Pigment Measurement —Clinical Applications .. . . . . . . . . . |
|
63 |
|
Frederik J.G.M. van Kuijk, Daniel Pauleikhoff |
|
|
7.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
63 |
7.2 |
Variability of Macula Pigment Distribution .. . . . . . . . . . . . . . . . . . . . . . . . |
|
63 |
7.3 |
Genetic and Environmental Factors of Macular Pigment Distribution |
|
65 |
7.4 |
Macular Pigment Distribution: Effect of Supplementation .. . . . . . . . . . |
|
66 |
7.5 |
Summary .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
67 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
68 |
|
Contents |
|
VII |
8 |
Evaluation of Fundus Autofluorescence Images . . . . . . . . . . . . . . . . . . |
|
71 |
|
Frank G. Holz, Monika Fleckenstein, Steffen Schmitz-Valckenberg, |
|
|
|
Alan C. Bird |
|
|
Part II Clinical Application .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
77 |
|
9 |
Macular and Retinal Dystrophies .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
79 |
|
Andrea von Rückmann, Fredrick W. Fitzke, |
|
|
|
Steffen Schmitz-Valckenberg, Andrew R. Webster, Alan C. Bird |
|
|
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
80 |
10 |
Discrete Lines of Increased Fundus Autofluorescence |
|
|
|
in Various Forms of Retinal Dystrophies .. . . . . . . . . . . . . . . . . . . . . . . . |
|
121 |
|
Monika Fleckenstein, Hendrik P.N. Scholl, Frank G. Holz |
|
|
10.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
121 |
10.2 |
Different Orientation of Lines of Increased FAF .. . . . . . . . . . . . . . . . . . . |
|
121 |
10.2.1 |
Orientation Along Retinal Veins .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
121 |
10.2.2 |
Ring Shape .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
122 |
10.3 |
Functional Correlate of Lines/Rings of Increased FAF .. . . . . . . . . . . . . |
|
122 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
124 |
11 |
Age-Related Macular Degeneration I—Early Manifestation . . . . . . |
|
133 |
|
Steffen Schmitz-Valckenberg, Hans-Martin Helb, |
|
|
|
Almut Bindewald-Wittich, Samantha S. Dandekar, Frank G. Holz |
|
|
11.1 |
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
133 |
11.2 |
FAF Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
133 |
11.3 |
Classification of FAF Patterns in Early AMD .. . . . . . . . . . . . . . . . . . . . . . |
|
135 |
11.4 |
Reticular Drusen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
135 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
136 |
12 |
Age-Related Macular Degeneration II—Geographic Atrophy .. . . . |
|
147 |
|
Steffen Schmitz-Valckenberg, Almut Bindewald-Wittich, |
|
|
|
Monika Fleckenstein, Hendrik P.N. Scholl, Frank G. Holz |
|
|
12.1 |
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
147 |
12.2 |
Detection and Quantification of Atrophy .. . . . . . . . . . . . . . . . . . . . . . . . . |
|
147 |
12.3 |
Correlation of FAF Findings with Functional Impairment . . . . . . . . . . |
|
148 |
12.4 |
Classification of FAF Patterns in Geographic Atrophy .. . . . . . . . . . . . . |
|
149 |
12.5 |
FAF Patterns and Progression Over Time .. . . . . . . . . . . . . . . . . . . . . . . . . |
|
149 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
|
151 |
VIII |
Contents |
|
|
13 |
Age-Related Macular Degeneration III—Pigment Epithelium |
|
|
|
Detachment .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
165 |
|
Felix Roth, Frank G. Holz |
|
|
13.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
165 |
13.2 |
FAF Findings .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
165 |
14 |
Age-Related Macular Degeneration IV—Choroidal |
|
|
|
Neovascularization (CNV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
179 |
|
Samantha S. Dandekar, Alan C. Bird |
|
|
14.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
179 |
14.2 |
FAF Findings in Early CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
180 |
14.3 |
FAF Findings in Late-Stage CNV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
180 |
14.4 |
FAF Findings in Relation to CNV Classification .. . . . . . . . . . . . . . . . |
. . . |
180 |
14.4.1 |
Classic CNV .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
181 |
14.4.2 |
Occult CNV .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
181 |
14.5 |
RPE Tears .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
182 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
182 |
15 |
Idiopathic Macular Telangiectasia .. . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
199 |
|
Peter Charbel Issa, Hendrik P.N. Scholl, Hans-Martin Helb, |
|
|
|
Frank G. Holz |
|
|
15.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
199 |
15.2 |
FAF in Type 1 Idiopathic Macular Telangiectasia .. . . . . . . . . . . . . . . |
. . . |
199 |
15.3 |
FAF in Type 2 Idiopathic Macular Telangiectasia .. . . . . . . . . . . . . . . |
. . . |
200 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
200 |
16 |
Chorioretinal Inflammatory Disorders . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
207 |
|
Richard F. Spaide |
|
|
16.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
207 |
16.2 |
Acute Posterior Multifocal Placoid Pigment Epitheliopathy .. . . . . |
. . . |
208 |
16.3 |
Acute Syphilitic Posterior Placoid Chorioretinitis .. . . . . . . . . . . . . . |
. . . |
209 |
16.4 |
Multifocal Choroiditis and Panuveitis .. . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
210 |
16.5 |
Acute Zonal Occult Outer Retinopathy .. . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
212 |
16.6 |
Birdshot Chorioretinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
213 |
|
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
214 |
17 |
Autofluorescence from the Outer Retina and Subretinal Space |
. . . |
241 |
|
Richard F. Spaide |
|
|
17.1 |
Introduction .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
241 |
17.2 |
Animal Models .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
242 |
17.3 |
Histopathology .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
243 |
17.4 |
Ocular Imaging .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . |
. . . |
244 |